The positively charged and relatively flexible PNA unit ethT (Fig. 1) has an ethylene linker between backbone and nucleobase rather than the methylene carbonyl linker normally present in PNA. The ...synthesis of the corresponding modified monomer, its incorporation into PNA oligomers, and their hybridization properties to DNA are described.
The positively charged and relatively flexible PNA unit ethT has an ethylene linker between backbone and nucleobase rather than the methylene carbonyl linker normally present in PNA. Hybridization properties of PNA oligomers incorporating this unit are reported.
A series of derivatives of 5-(aminomethyl)-8-methoxypsoralens, 8-(3-aminopropyl)oxypsoralens, and 5-3-(tri-methylammonio)propylmethyl-8-methoxypsoralen has been synthesized and their potential as ...PUVA reagents examined. While the DNA association constants of selected psoralens were found to be 10(5)-10(6)L mol-1, corresponding to efficient binding, flow linear dichroism studies indicated that only the 8-substituted psoralens bind to DNA by intercalation. Furthermore, the ability to photoinduce interstrand cross-links in calf thymus DNA, in vitro, was as efficient as that of 8-methoxypsoralen for the 8-substituted psoralens, which were up to 25 times as efficient as the 5-substituted psoralens. Four of the psoralens studied were radiolabeled and used to study photobinding to DNA. Analogously to the cross-binding results, the 8-substituted psoralens were more efficiently photobound than the 5-substituted, while only slight differences were found in the photobinding-cross-linking ratio. The photoreactivity of the aminopsoralens toward cyclohexene and 2'-deoxythymidine was enhanced compared to that of 8-methoxypsoralen, the effect being most pronounced when the amino group is close to the furocoumarin ring system. Most of the new compounds were less photocytotoxic than 8-methoxypsoralen to NHIK 3025 cells, in vitro, and they caused less light-induced DNA interstrand cross-linking, in situ, in these cells. A clear correlation between the photocytotoxicity and the DNA cross-linking ability of the psoralens was observed. Several of the derivatives showed more pronounced effects in the light-dependent skin thickening (inflammatory) test on mice than 8-methoxypsoralen. No correlation between DNA cross-linking capacity, in vitro, and skin phototoxicity was found for this series of psoralens.
Novel PNA oligomers containing an
N-(aminomethyl) β-alanine backbone (‘retroinverso’ PNA) were prepared
via blocksynthesis or
via a combination of solution and solid-phase chemistry. The half-life ...time of the unprotected N terminus is 38 h at pH 7.0 (20 °C) and is pH dependent.
N-(2-benzyloxyethyl)-
N-(thymin-1-ylacetyl)glycine was synthesised and used as a linker for coupling DNA and PNA together. Three different 10-mers composed of 6 DNA units and 4 PNA thymine units were ...made. The PNA-DNA chimera hybridise to complementary DNA or PNA oligomers, and both the PNA and the DNA part of the chimera are involved in the binding.
N-(2-benzyloxyethyl)-
N-(thymin-1-ylacetyl)glycine was synthesised and used as a linker for coupling DNA and PNA together. Three different 10-mers were made. They all hybridise to the complementary DNA or PNA and both parts of the chimera are involved in the binding.
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